Natural Killer Cells and Solid Tumors

Abstract

Natural killer (NK) cells play an important role in the innate immune response against cancer, in particular in the elimination of tumor metastases and small tumors. NK cell-mediated control of large solid tumors is usually not efficient, although tumors often express high amounts of activating ligands and low levels of inhibitory ligands, such as MHC class I. Thus, we assume that these tumors might be good targets for NK cell-mediated attack. In vitro, NK cells directly kill tumor cells and release soluble factors that affect both innate and adaptive immune responses. To date, in vivo NK cell activation during tumor progression, the influence of the tumor microenvironment on NK cells, and the mechanisms that interfere with their effector function in cancer patients are not completely understood. This review summarizes our current knowledge of NK cells in solid tumors. We will discuss the impact of novel insights into NK cell responses against tumors on the design of NK cell-based therapies.

Is the Tumor Infiltrating Natural Killer Cell (NK-TILs) Count in Infiltrating Ductal Carcinoma of Breast Prognostically Significant?

“…Compared with blood NK cells, only a limited amount of information is available on tissue infiltrating NK-TILs in breast cancer (Jochems and Schlom, 2011), which usually present more severe phenotypic and functional alterations compared with circulating or non-cancerous tissue-infiltrating NK counterparts (Fregni et al, 2012). Although the number of NK cells coming into contact with neoplastic cells constitute a small percentage of the infiltrating lymphocytes, they can play an important role in the prognosis of tumors (Stojanovic and Cerwenka, 2011).…”

Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments

“…1 In most of studies, functionally impaired NK-cells have been isolated from tumors, and their defective function appears to be associated with cancer progression. 2 Evidence in HCC showed decreased NK subset in peripheral blood and in tumor compared to non-tumor liver tissue. 3,4 In addition, functional defects such as impaired cytokine production and killing [3][4][5][6] were observed, mainly in NK-cells from patients with advanced stage HCC, 4 and were shown to represent a negative prognostic factor after hepatectomy.…”

NK Cells Are Required for Dendritic Cell–Based Immunotherapy at the Time of Tumor Challenge

“…NK cells detect and destroy malignant and virally infected cells (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Aside from their cytotoxic abilities against low MHC-I tumor cells, interactions between NK cells and DC have been shown to result in the activation of a helper NK cell phenotype, characterized by the production of IFN-g and associated with enhanced CTL and Th1 responses (15,16,(25)(26)(27)(28)(29).…”

“…Aside from their cytotoxic abilities against low MHC-I tumor cells, interactions between NK cells and DC have been shown to result in the activation of a helper NK cell phenotype, characterized by the production of IFN-g and associated with enhanced CTL and Th1 responses (15,16,(25)(26)(27)(28)(29). NK cells also possess adaptive features (30), and the NK cell subset responsible for memory-like responses was recently shown to be a liver-derived CD49b lo /NK1.1 hi subset (31).…”

“…IFN-g has been shown to be a key effector cytokine in antitumor responses, directly affecting tumor cells by decreasing proliferation and metabolic activity, enhancing costimulator molecule and MHC expression, as well as inhibiting angiogenesis by tumor cells through induction of CXC chemokines (13,14,16,32). Adjusting DC-based therapies to augment NK cell function and IFN-g secretion could therefore complement current CD8 T cell strategies in controlling tumor growth (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”